Fire ants (solenopsis spp.) are a pest of economic and medical significance in the United States in part due to the painful, and sometimes dangerous, sting they inflict. We have demonstrated that histamine release from mast cells plays a major role in the action of fire ant venoms in the whole animal. A synthetic venom component, cis-2-methyl-6-undecylpiperidine, also causes histamine release. Release of histamine occurs concurrently with release of lactic acid dehydrogenase, a cytoplasmic enzyme, suggesting lysis as a mechanism at the cellular level. We propose to determine the extent to which the piperidine components of the venom are responsible for the effects of fire ant stings, to investigate whether the antimicrobial activity of the venom is also due to membrane disruption, to synthesize additional venom piperidines and related compounds and study their structure-activity relations for histamine- and LDH-release from mast cells, antimicrobial and enzyme releasing activity in microorganisms, and hemolysis of red blood cells. More detailed understanding of the interaction of these agents with the membrane will be obtained through electron spin resonance and scanning electron microscope studies of red blood cell membranes in the presence and absence of the venoms and piperidines.